A Novel Hybrid of Chloroquine and Primaquine Linked by Gold(I): Multitarget and Multiphase Antiplasmodial Agent
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2021 |
| Outros Autores: | , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/49041 |
Resumo: | [a] C. de Souza Pereira, V. Schmitz, Prof. H. F. Dos Santos, Prof. M. Navarro Departamento de Química Universidade Federal de Juiz de Fora, Rua José Lourenço Kelmer, s/n – Campus Universitário, Bairro Martelos CEP 36036-900, Juiz de Fora, Minas Gerais (Brasil) E-mail: maribel.navarro@ufjf.edu.br [b] H. Costa Quadros, Dr. D. R. Magalhaes Moreira, R. I. Santos De Deus Da Silva, Dr. M. Botelho Pereira Soares Instituto Gonçalo Moniz Fundação Oswaldo Cruz, Av. Waldemar Falcão, 121, Candeal, Salvador, Bahia (Brasil) [c] Dr. W. Castro Centro de Química Instituto Venezolano de Investigaciones Científicas (IVIC), Centro de Química, Carretera Panamericana, Km 11, Altos de Pipe, San Antonio de los Altos Miranda, 1020-A, Caracas (Venezuela) [d] Dr. D. Fontinha, Dr. M. Prudêncio Instituto de Medicina Molecular João Lobo Antunes Faculdade de Medicina, Universidade de Lisboa <Lisboa (Portugal) [e] M. Gendrot, I. Fonta, J. Mosnier, Dr. B. Pradines Unité Parasitologie et entomologie, Institut de recherche biomédicale des armées, 19–21 Bd Jean Moulin, 13005 Marseille (France) [f] M. Gendrot, I. Fonta, J. Mosnier, Dr. B. Pradines Aix-Marseille Univ, IRD, SSA, AP-HM, VITROME, 19–21 Bd Jean Moulin, 13005 Marseille (France) [g] M. Gendrot, I. Fonta, J. Mosnier, Dr. B. Pradines IHU Méditerranée Infection, 19–21 Bd Jean Moulin, 13005 Marseille (France) [h] I. Fonta, J. Mosnier, Dr. B. Pradines Centre National de Référence du Paludisme, 19–21 Bd Jean Moulin, 13005 Marseille (France) |
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Pereira, Caroline de SouzaQuadros, Helenita CostaMoreira, Diogo Rodrigo MagalhaesCastro, WilliamSilva, Romulo Ivisson Santos de Deus daSoares, Milena Botelho PereiraFontinha, DianaPrudêncio, MiguelSchmitz, ViniciusSantos, Hélio F. dosGendrot, MathieuFonta, IsabelleMosnier, JoelPradines, BrunoNavarro, Maribel2021-09-08T13:25:11Z2021-09-08T13:25:11Z2021PEREIRA, Caroline de Souza et al. A Novel Hybrid of Chloroquine and Primaquine Linked by Gold(I): Multitarget and Multiphase Antiplasmodial Agent. ChemMedChem, 2021.1860-7179https://www.arca.fiocruz.br/handle/icict/4904110.1002/cmdc.202000653[a] C. de Souza Pereira, V. Schmitz, Prof. H. F. Dos Santos, Prof. M. Navarro Departamento de Química Universidade Federal de Juiz de Fora, Rua José Lourenço Kelmer, s/n – Campus Universitário, Bairro Martelos CEP 36036-900, Juiz de Fora, Minas Gerais (Brasil) E-mail: maribel.navarro@ufjf.edu.br [b] H. Costa Quadros, Dr. D. R. Magalhaes Moreira, R. I. Santos De Deus Da Silva, Dr. M. Botelho Pereira Soares Instituto Gonçalo Moniz Fundação Oswaldo Cruz, Av. Waldemar Falcão, 121, Candeal, Salvador, Bahia (Brasil) [c] Dr. W. Castro Centro de Química Instituto Venezolano de Investigaciones Científicas (IVIC), Centro de Química, Carretera Panamericana, Km 11, Altos de Pipe, San Antonio de los Altos Miranda, 1020-A, Caracas (Venezuela) [d] Dr. D. Fontinha, Dr. M. Prudêncio Instituto de Medicina Molecular João Lobo Antunes Faculdade de Medicina, Universidade de Lisboa <Lisboa (Portugal) [e] M. Gendrot, I. Fonta, J. Mosnier, Dr. B. Pradines Unité Parasitologie et entomologie, Institut de recherche biomédicale des armées, 19–21 Bd Jean Moulin, 13005 Marseille (France) [f] M. Gendrot, I. Fonta, J. Mosnier, Dr. B. Pradines Aix-Marseille Univ, IRD, SSA, AP-HM, VITROME, 19–21 Bd Jean Moulin, 13005 Marseille (France) [g] M. Gendrot, I. Fonta, J. Mosnier, Dr. B. Pradines IHU Méditerranée Infection, 19–21 Bd Jean Moulin, 13005 Marseille (France) [h] I. Fonta, J. Mosnier, Dr. B. Pradines Centre National de Référence du Paludisme, 19–21 Bd Jean Moulin, 13005 Marseille (France)CAPES (grant no. 23038.006713/2013-88), CNPq (grant no. 305732/2019- 6), FAPES grant number APP0088/2016) and Fiocruz/Inova (grant no.1642178247). MP was supported by grant PTDC-SAU-INF- 29550-2017 (FCT, Portugal). HFDS and VS also thankful to FAPEMIG for the purchase of Nvidia graphics processing unit (GPU) used to speed up the MD simulations. CSP thanks CAPES for her Ph.D. scholarship."Múltipla ver em Notas"Plasmodium parasites kill 435 000 people around the world every year due to unavailable vaccines, a limited arsenal of antimalarial drugs, delayed treatment, and the reduced clinical effectiveness of current practices caused by drug resistance. Therefore, there is an urgent need to discover and develop new antiplasmodial candidates. In this work, we present a novel strategy to develop a multitarget metallic hybrid antimalarial agent with possible dual efficacy in both sexual and asexual erythrocytic stages. A hybrid of antimalarial drugs (chloroquine and primaquine) linked by gold(I) was synthesized and characterized by spectroscopic and analytical techniques. The CQPQ-gold(I) hybrid molecule affects essential parasite targets, it inhibits β-hematin formation and interacts moderately with the DNA minor groove. Its interaction with PfTrxR was also examined in computational modeling studies. The CQPQ-gold(I) hybrid displayed an excellent in vitro antimalarial activity against the blood-stage of Plasmodium falciparum and liverstage of Plasmodium berghei and efficacy in vivo against P. berghei, thereby demonstrating its multiple-stage antiplasmodial activity. This metallic hybrid is a promising chemotherapeutic agent that could act in the treatment, prevention, and transmission of malariaengWileyCloriquinaPrimaquinaMalariaPlasmodiumResistência a medicamnetosTratamentoChloroquinePrimaquineMalariaPlasmodiumDrug resistanceTreatmentA Novel Hybrid of Chloroquine and Primaquine Linked by Gold(I): Multitarget and Multiphase Antiplasmodial Agentinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83097https://www.arca.fiocruz.br/bitstream/icict/49041/1/license.txt36b51ef91c52b5338d9d29ba0cc807bcMD51ORIGINALPereira, Caroline de Souza A novel hybrid....pdfPereira, Caroline de Souza A novel 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| dc.title.pt_BR.fl_str_mv |
A Novel Hybrid of Chloroquine and Primaquine Linked by Gold(I): Multitarget and Multiphase Antiplasmodial Agent |
| title |
A Novel Hybrid of Chloroquine and Primaquine Linked by Gold(I): Multitarget and Multiphase Antiplasmodial Agent |
| spellingShingle |
A Novel Hybrid of Chloroquine and Primaquine Linked by Gold(I): Multitarget and Multiphase Antiplasmodial Agent Pereira, Caroline de Souza Cloriquina Primaquina Malaria Plasmodium Resistência a medicamnetos Tratamento Chloroquine Primaquine Malaria Plasmodium Drug resistance Treatment |
| title_short |
A Novel Hybrid of Chloroquine and Primaquine Linked by Gold(I): Multitarget and Multiphase Antiplasmodial Agent |
| title_full |
A Novel Hybrid of Chloroquine and Primaquine Linked by Gold(I): Multitarget and Multiphase Antiplasmodial Agent |
| title_fullStr |
A Novel Hybrid of Chloroquine and Primaquine Linked by Gold(I): Multitarget and Multiphase Antiplasmodial Agent |
| title_full_unstemmed |
A Novel Hybrid of Chloroquine and Primaquine Linked by Gold(I): Multitarget and Multiphase Antiplasmodial Agent |
| title_sort |
A Novel Hybrid of Chloroquine and Primaquine Linked by Gold(I): Multitarget and Multiphase Antiplasmodial Agent |
| author |
Pereira, Caroline de Souza |
| author_facet |
Pereira, Caroline de Souza Quadros, Helenita Costa Moreira, Diogo Rodrigo Magalhaes Castro, William Silva, Romulo Ivisson Santos de Deus da Soares, Milena Botelho Pereira Fontinha, Diana Prudêncio, Miguel Schmitz, Vinicius Santos, Hélio F. dos Gendrot, Mathieu Fonta, Isabelle Mosnier, Joel Pradines, Bruno Navarro, Maribel |
| author_role |
author |
| author2 |
Quadros, Helenita Costa Moreira, Diogo Rodrigo Magalhaes Castro, William Silva, Romulo Ivisson Santos de Deus da Soares, Milena Botelho Pereira Fontinha, Diana Prudêncio, Miguel Schmitz, Vinicius Santos, Hélio F. dos Gendrot, Mathieu Fonta, Isabelle Mosnier, Joel Pradines, Bruno Navarro, Maribel |
| author2_role |
author author author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Pereira, Caroline de Souza Quadros, Helenita Costa Moreira, Diogo Rodrigo Magalhaes Castro, William Silva, Romulo Ivisson Santos de Deus da Soares, Milena Botelho Pereira Fontinha, Diana Prudêncio, Miguel Schmitz, Vinicius Santos, Hélio F. dos Gendrot, Mathieu Fonta, Isabelle Mosnier, Joel Pradines, Bruno Navarro, Maribel |
| dc.subject.other.pt_BR.fl_str_mv |
Cloriquina Primaquina Malaria Plasmodium Resistência a medicamnetos Tratamento |
| topic |
Cloriquina Primaquina Malaria Plasmodium Resistência a medicamnetos Tratamento Chloroquine Primaquine Malaria Plasmodium Drug resistance Treatment |
| dc.subject.en.pt_BR.fl_str_mv |
Chloroquine Primaquine Malaria Plasmodium Drug resistance Treatment |
| description |
[a] C. de Souza Pereira, V. Schmitz, Prof. H. F. Dos Santos, Prof. M. Navarro Departamento de Química Universidade Federal de Juiz de Fora, Rua José Lourenço Kelmer, s/n – Campus Universitário, Bairro Martelos CEP 36036-900, Juiz de Fora, Minas Gerais (Brasil) E-mail: maribel.navarro@ufjf.edu.br [b] H. Costa Quadros, Dr. D. R. Magalhaes Moreira, R. I. Santos De Deus Da Silva, Dr. M. Botelho Pereira Soares Instituto Gonçalo Moniz Fundação Oswaldo Cruz, Av. Waldemar Falcão, 121, Candeal, Salvador, Bahia (Brasil) [c] Dr. W. Castro Centro de Química Instituto Venezolano de Investigaciones Científicas (IVIC), Centro de Química, Carretera Panamericana, Km 11, Altos de Pipe, San Antonio de los Altos Miranda, 1020-A, Caracas (Venezuela) [d] Dr. D. Fontinha, Dr. M. Prudêncio Instituto de Medicina Molecular João Lobo Antunes Faculdade de Medicina, Universidade de Lisboa <Lisboa (Portugal) [e] M. Gendrot, I. Fonta, J. Mosnier, Dr. B. Pradines Unité Parasitologie et entomologie, Institut de recherche biomédicale des armées, 19–21 Bd Jean Moulin, 13005 Marseille (France) [f] M. Gendrot, I. Fonta, J. Mosnier, Dr. B. Pradines Aix-Marseille Univ, IRD, SSA, AP-HM, VITROME, 19–21 Bd Jean Moulin, 13005 Marseille (France) [g] M. Gendrot, I. Fonta, J. Mosnier, Dr. B. Pradines IHU Méditerranée Infection, 19–21 Bd Jean Moulin, 13005 Marseille (France) [h] I. Fonta, J. Mosnier, Dr. B. Pradines Centre National de Référence du Paludisme, 19–21 Bd Jean Moulin, 13005 Marseille (France) |
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2021 |
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2021-09-08T13:25:11Z |
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2021-09-08T13:25:11Z |
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2021 |
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info:eu-repo/semantics/article |
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PEREIRA, Caroline de Souza et al. A Novel Hybrid of Chloroquine and Primaquine Linked by Gold(I): Multitarget and Multiphase Antiplasmodial Agent. ChemMedChem, 2021. |
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https://www.arca.fiocruz.br/handle/icict/49041 |
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1860-7179 |
| dc.identifier.eissn.none.fl_str_mv |
10.1002/cmdc.202000653 |
| identifier_str_mv |
PEREIRA, Caroline de Souza et al. A Novel Hybrid of Chloroquine and Primaquine Linked by Gold(I): Multitarget and Multiphase Antiplasmodial Agent. ChemMedChem, 2021. 1860-7179 10.1002/cmdc.202000653 |
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eng |
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info:eu-repo/semantics/openAccess |
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Wiley |
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Wiley |
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